The Role of Indirect Recognition of MHC Class I and II Allopeptides in a Fully Mismatched Miniature Swine Model of Lung Transplantation

H. Sahara, T. Shoji, C. Y. Ng, M. J. Weiss, A. Muniappan, D. A. Guenther, S. L. Houser, A. C. Pujara, J. K. Sayre, J. C. Wain, D. H. Sachs, J. C. Madsen, J. S. Allan

Research output: Contribution to journalArticle

Abstract

Considerable evidence suggests that indirect recognition of MHC allopeptides plays an important role in solid-organ rejection. Here, we examine whether immunization with class I or class II allopeptides accelerates rejection in a fully MHC-mismatched lung transplant model in miniature swine. Methods: Recipients were immunized with either donor-derived class I or class II peptides. Sensitization to the peptides was confirmed by DTH testing and in vitro proliferation assays. Nonimmunized control (n = 6), class I peptide-immunized (n = 3), and class II peptide-immunized (n = 3) swine were transplanted with fully mismatched lungs using only a 12-day course of tacrolimus. Results: One control animal rejected its graft on postoperative day 103, while the others maintained their grafts for over 1 year. In the class I peptide-immunized group, two recipients rejected their grafts (days 14 and 52). The third animal has not rejected the graft (day 120, experiment is ongoing). In contrast, in the class II-peptide immunized group, only one animal rejected its graft on day 52, while the others maintained their grafts over 1 year. Both anti-donor IgM and IgG antibodies were detectable in all acute rejectors, although no alloantibody was detectable in long-term acceptors. Regardless of the fate of the graft, all animals have maintained their proliferative responses to the peptides. However, only acceptors maintained donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity and mixed lymphocyte reaction assays. Conclusions: Pretransplant sensitization of lung allograft recipients to donor allopeptides accelerates graft rejection. This appears particularly true for class I-derived allopeptides, suggesting that class II molecules may be less antigenic when presented indirectly.

Original languageEnglish (US)
Pages (from-to)3256-3258
Number of pages3
JournalTransplantation proceedings
Volume38
Issue number10
DOIs
StatePublished - Dec 1 2006

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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    Sahara, H., Shoji, T., Ng, C. Y., Weiss, M. J., Muniappan, A., Guenther, D. A., Houser, S. L., Pujara, A. C., Sayre, J. K., Wain, J. C., Sachs, D. H., Madsen, J. C., & Allan, J. S. (2006). The Role of Indirect Recognition of MHC Class I and II Allopeptides in a Fully Mismatched Miniature Swine Model of Lung Transplantation. Transplantation proceedings, 38(10), 3256-3258. https://doi.org/10.1016/j.transproceed.2006.10.059